Group A streptococcus (“GAS,” S. pyogenes) is a frequent human pathogen, estimated to be present in between 5-15% of normal individuals without signs of disease. An acute infection occurs, however, when host defenses are compromised, when the organism is able to exert its virulence, or when the organism is introduced to vulnerable tissues or hosts. Related diseases include puerperal fever, scarlet fever, erysipelas, pharyngitis, impetigo, necrotizing fasciitis, myositis, and streptococcal toxic shock syndrome.
GAS bacteria are gram positive, non-spore forming coccus-shaped bacteria which typically exist in chains or in pairs of cells. GAS bacteria are subdivided according to serotyping based on a large, highly variable cell surface antigen call the M protein. Lancefield, J. Exp. Med. 47, 9-10, 1928; Lancefield, J. Immunol. 89, 307-13, 1962. DNA sequencing of genes encoding M proteins has become the most common method of determining GASM types (emm sequence types). To date 124 different M types have been identified; 22 of these types were identified between 1995 and 1998 (Facklam et al., Clin. Infect. Dis. 34, 28-38, 2002). M1, M28, M12, M3, M11, and M6 are among the most prevalent GAS types worldwide. Li et al., Infect. Dis. 188, 1587-92, 2003; O'Brien et al., Clin. Infect. Dis. 35, 268-76, 2002.
Although S. pyogenes infections can be treated using antibiotics, there is a need in the art for prophylactic vaccines to prevent the onset of disease, as well as for additional therapies for treating S. pyogenes infections.